Many aspects of affective illness, including depression, involve a disturbance in the limbic-cortical emotional circuitry. A persistent or inappropriate activation of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis is observed in many of these conditions. The comprehensive goal of this Level I Network application, Prenatal and Perinatal Experience and Children's Mental Health, is to strengthen the conceptual and empirical linkages between: 1) rodent, sheep and non-human primate research on adverse early experiences and development of the LHPA axis, and 2) human research on the emotional and cognitive sequelae of early adversity experiences during the fetal, perinatal and/or early neonatal period. Our enduring goal is to develop collaborative research programs designed to study the long-term effects of adverse fetal and early neonatal experience on the neurobiology of LHPA development in relation to cognitive and emotional function in infants, children and adolescents, particularly in relation to vulnerability to mental illness. We specifically hypothesize that alterations in key elements of the LHPA axis that can be initiated in utero and or in the perinatal period may be brought about by a variety of adverse environmental conditions. Given an appropriate genetic substrate, such adverse early life experiences may create a neurobiological foundation that leads to vulnerability to mental illness. By integrating the diverse expertise provided by the assembled group of invited researchers, our objective is to develop animal paradigms that appropriately model the molecular and neurobiological processes underlying effects of fetal and neonatal adversity on LHPA development in the human. Such discussions will inevitably provide the background necessary to develop a means to measure human response patterns to fetal and/or neonatal adversity. Four conceptual topics have been identified that form the specific aims this network. These topics are: 1) Prenatal and perinatal animal models and their validity to the human condition, 2) Developmental windows and equivalency across species, 3) In utero and/or perinatal adverse experiences and long term sequelae: the role of key elements of the LHPA axis, and 4) Individual differences with respect to genetic vulnerability, and resilience, to mental illness. We have used these to organize the first 5 of the 9 planned network meetings, with the last 3 meetings devoted to discussing and refining research and grant proposal plans. Twelve network members, spanning expertise from molecular to behavioral and epidemiological levels in rodent, sheep, monkey, and human fetal and infant populations have been assembled, along with two consultants who will join the group for specified topics and meetings. Network members are: Charles R. Neal and Delia M. Vaizquez (Co-PI's), K. Sunny Anand, Ronald G. Barr, Alice S. Carter, Christopher Coe, Michael K. Georgieff, Vivette Glover, Kate Keenan, Michael S. Kramer, Peter Nathanielsz and Pathik Wadhwa. The consultants are Megan Gunnar and Seymour Levine. The proposed network will ultimately foster hypothesis driven research initiatives, and develop new strategies that will effectively test the impact of adverse fetal and neonatal experience on LHPA development, bridging clinical obstetrics and neonatology, epidemiology, developmental neuroanatomy and neurosciences with mental illness in children and adolescents.